Maternal transmission of Alzheimer's disease: Prodromal metabolic phenotype and the search for genes

Alzheimer's disease (AD) is the most common form of dementia in late life, affecting approximately 10 per cent of individuals of 65 years of age, with the prevalence doubling every five years up to the age of 80, above which the prevalence is 40 per cent [1]. In 2008, in the United States alone, there were more than 5 million people with AD, which is a 10 per cent increase from the previous (in 2000) prevalence estimate of 4.5 million (Figure 1, adapted from Hebert et al.[2]). Age-related mild cognitive impairments may affect two to three times as many individuals [3,4]. By 2050, the number of elderly people with AD in the USA could range from 11 million to 16 million, which strongly calls for strategies to prevent or delay the onset of the disease.AD is a neurodegenerative disorder characterised by global deficits in cognition, ranging from memory loss to impaired judgment and reasoning [5]. Clinical diagnosis per se is often uncertain and clinical assessment requires multiple examinations and laboratory tests over time. Despite thorough clinical exams, the frequency of unrecognised dementia in the community ranges from 50 per cent to 90 per cent of cases [6]. Insidious onset and progressive impairment of memory and other cognitive functions make the initial stages of AD difficult to distinguish from so called 'normal ageing'. In order to develop prevention treatments for AD, it is necessary to identify persons who are still cognitively normal (NL), but are either at very high risk for developing the disease or are in an early, pre-symptomatic stage of the disease. Such individuals are most likely to benefit from therapies which are instituted when the potential for preservation of function is the greatest, well before irreversible synaptic and neuronal injury.The difficulty in studying the genetics of complex, age-associated disorders such as late onset AD (LOAD) using traditional clinical case identification measures has resulted in an increasing emphasis on stud